First measurements with the CMS DAQ and timing hub prototype-1

The DAQ and Timing Hub is an ATCA hub board designed for the Phase-2 upgrade of the CMS experiment. In addition to providing high-speed Ethernet connectivity to all back-end boards, it forms the bridge between the sub-detector electronics and the central DAQ, timing, and trigger control systems. One important requirement is the distribution of several high-precision, phasestable, and LHC-synchronous clock signals for use by the timing detectors. The current paper presents first measurements performed on the initial prototype, with a focus on clock quality. It is demonstrated that the current design provides adequate clock quality to satisfy the requirements of the Phase-2 CMS timing detectors

Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats

The aim of this study was to examine oxidative load and endothelium-dependent vasorelaxation in the serotonin pre-constricted femoral artery (FA) of Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding in the presence or absence of ascorbic acid (AsA) in working solution. Adult male rats were randomly divided into control (living space: 480 cm2/rat) or stressed (living space: 200 cm2/rat) groups for 8 weeks. Blood pressure and heart rate, determined using tail-cuff plethysmography, were not influenced by stress vs. control. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured in the left ventricle and liver (for assessment of oxidative load) and were found unchanged by chronic crowding. The nitric oxide (NO)-dependent component of endothelium-dependent relaxation was investigated in the FA using a wire myograph. In both the presence and absence of AsA, acetylcholine-induced relaxation of the FA of stressed rats significantly exceeded that of the controls, which was associated with an increase of the NO-dependent component. In conclusion, the data showed that chronic crowding did not produce oxidative stress in the organs investigated and indicate that elevation of NO production during chronic stress is an important way of adaptation, which may prevent normotensive rats from the development of stress-induced hypertension

Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem

Optimism as a Prior Belief about the Probability of Future Reward

Optimists hold positive a priori beliefs about the future. In Bayesian statistical theory, a priori beliefs can be overcome by experience. However, optimistic beliefs can at times appear surprisingly resistant to evidence, suggesting that optimism might also influence how new information is selected and learned. Here, we use a novel Pavlovian conditioning task, embedded in a normative framework, to directly assess how trait optimism, as classically measured using self-report questionnaires, influences choices between visual targets, by learning about their association with reward progresses. We find that trait optimism relates to an a priori belief about the likelihood of rewards, but not losses, in our task. Critically, this positive belief behaves like a probabilistic prior, i.e. its influence reduces with increasing experience. Contrary to findings in the literature related to unrealistic optimism and self-beliefs, it does not appear to influence the iterative learning process directly

Structural and evolutionary classification of Type II restriction enzymes based on theoretical and experimental analyses

For a very long time, Type II restriction enzymes (REases) have been a paradigm of ORFans: proteins with no detectable similarity to each other and to any other protein in the database, despite common cellular and biochemical function. Crystallographic analyses published until January 2008 provided high-resolution structures for only 28 of 1637 Type II REase sequences available in the Restriction Enzyme database (REBASE). Among these structures, all but two possess catalytic domains with the common PD-(D/E)XK nuclease fold. Two structures are unrelated to the others: R.BfiI exhibits the phospholipase D (PLD) fold, while R.PabI has a new fold termed ‘half-pipe’. Thus far, bioinformatic studies supported by site-directed mutagenesis have extended the number of tentatively assigned REase folds to five (now including also GIY-YIG and HNH folds identified earlier in homing endonucleases) and provided structural predictions for dozens of REase sequences without experimentally solved structures. Here, we present a comprehensive study of all Type II REase sequences available in REBASE together with their homologs detectable in the nonredundant and environmental samples databases at the NCBI. We present the summary and critical evaluation of structural assignments and predictions reported earlier, new classification of all REase sequences into families, domain architecture analysis and new predictions of three-dimensional folds. Among 289 experimentally characterized (not putative) Type II REases, whose apparently full-length sequences are available in REBASE, we assign 199 (69%) to contain the PD-(D/E)XK domain. The HNH domain is the second most common, with 24 (8%) members. When putative REases are taken into account, the fraction of PD-(D/E)XK and HNH folds changes to 48% and 30%, respectively. Fifty-six characterized (and 521 predicted) REases remain unassigned to any of the five REase folds identified so far, and may exhibit new architectures. These enzymes are proposed as the most interesting targets for structure determination by high-resolution experimental methods. Our analysis provides the first comprehensive map of sequence-structure relationships among Type II REases and will help to focus the efforts of structural and functional genomics of this large and biotechnologically important class of enzymes

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architecture for rational agents interacting wit

Best-fitting parameters for the Bayesian model summarized per experiment and averaged for the entire group of subjects and per subgroup (optimists and pessimists).

<p>Each column presents the mean value, with the standard deviation between brackets. Significance of the differences is shown on the right of the table: an asterisk in the corresponding column (left to right: LOT-R; α/(α+β) which defines where the prior is centered; γ is the softmax decision parameter) indicates a p value less than 0.05 for a t-test between optimists and pessimists.</p

a) Cartoon of the task: subjects are presented with a sequence of stimuli (here: O₁, O₂, O₁) followed by a decision screen (D₁).

<p>Here the subject needs to choose between the yellow fractal and the square for which the reward probability is given by the number of blue dots (6 dots, indicating a probability of 60%). <u>Inset:</u> Example of a longer sequence of interleaved observation screens and decision screens. <b>b</b>) Performance of the subjects (% trials in which they chose the fractal stimulus) as a function of the difference between the observed reward rate of the fractal being considered and the reward probability of the square. Compared to pessimistic people (red, LOT-R≤mean LOT-R), optimistic people (blue, LOT-R>mean LOT-R) tend to overestimate the probability of reward associated with the uncertain fractal stimulus. Errors bars denote standard deviation. <b>c</b>) Correlation between subjects' LOT-R scores and the mean of their prior distribution p(c) that the fractal stimulus will lead to a reward (r = 0.438, p = 0.001). <b>d</b>) Examples of the prior distributions that were extracted for subjects 10 (pessimistic, LOT-R = 3) and 11 (optimistic, LOT-R = 22) based on their task performance.</p